Avoiding Tacrolimus Underexposure and Overexposure with a Dosing Algorithm for Renal Transplant Recipients: A Single Arm Prospective Intervention Trial
Clinical Pharmacology & Therapeutics, vol. 110, pp. 169–178
Abstract
Bodyweight‐based tacrolimus dosing followed by therapeutic drug monitoring is standard clinical care after renal transplantation. However, after transplantation, a meager 38% of patients are on target at first steady‐state and it can take up to 3 weeks to reach the target tacrolimus predose concentration (C0). Tacrolimus underexposure and overexposure is associated with an increased risk of rejection and drug‐related toxicity, respectively. To minimize subtherapeutic and supratherapeutic tacrolimus exposure in the immediate post‐transplant phase, a previously developed dosing algorithm to predict an individual’s tacrolimus starting dose was tested prospectively. In this single‐arm, prospective, therapeutic intervention trial, 60 de novo kidney transplant recipients received a tacrolimus starting dose based on a dosing algorithm instead of a standard, bodyweight‐based dose. The algorithm included cytochrome P450 (CYP)3A4 and CYP3A5 genotype, body surface area, and age as covariates. The target tacrolimus C0, measured for the first time at day 3, was 7.5–12.5 ng/mL. Between February 23, 2019, and July 7, 2020, 60 patients were included. One patient was excluded because of a protocol violation. On day 3 post‐transplantation, 34 of 59 patients (58%, 90% CI 47–68%) had a tacrolimus C0 within the therapeutic range. Markedly subtherapeutic (< 5.0 ng/mL) and supratherapeutic (> 20 ng/mL) tacrolimus concentrations were observed in 7% and 3% of the patients, respectively. Biopsy‐proven acute rejection occurred in three patients (5%). In conclusion, algorithm‐based tacrolimus dosing leads to the achievement of the tacrolimus target C0 in as many as 58% of the patients on day 3 after kidney transplantation.
Authors 10
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Marith I. Francke corresponding
Affiliation as printed
Department of Internal Medicine Division of Nephrology and Transplantation Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
Netherlands Institute for Health Sciences Rotterdam The Netherlands
Rotterdam Transplant Group Rotterdam The Netherlands
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Netherlands Institute for Health Sciences, Rotterdam, The Netherlands
Rotterdam Transplant Group, Rotterdam, The Netherlands
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Erasmus MC · Meander Medisch Centrum
Affiliation as printed
Department of Hospital Pharmacy Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
Department of Hospital Pharmacy Meander Medical Center Amersfoort The Netherlands
Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Hospital Pharmacy, Meander Medical Center, Amersfoort, The Netherlands
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Affiliation as printed
Department of Hospital Pharmacy Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
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Affiliation as printed
Department of Internal Medicine Division of Nephrology and Transplantation Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
Rotterdam Transplant Group Rotterdam The Netherlands
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam Transplant Group, Rotterdam, The Netherlands
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Affiliation as printed
Department of Pathology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
Rotterdam Transplant Group Rotterdam The Netherlands
Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam Transplant Group, Rotterdam, The Netherlands
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Teun van Gelder Aachen Department of Clinical Pharmacy and Toxicology Leiden University Medical Center Leiden The Netherlands Department of Clinical Pharmacy and Toxicology
Leiden University Medical Center
Affiliation as printed
Department of Clinical Pharmacy and Toxicology Leiden University Medical Center Leiden The Netherlands
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Department of Clinical Chemistry Erasmus MC University Medical Center Rotterdam The Netherlands
Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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Affiliation as printed
Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands
Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Affiliation as printed
Department of Hospital Pharmacy Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
Rotterdam Transplant Group Rotterdam The Netherlands
Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam Transplant Group, Rotterdam, The Netherlands
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Affiliation as printed
Department of Internal Medicine Division of Nephrology and Transplantation Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
Rotterdam Transplant Group Rotterdam The Netherlands
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam Transplant Group, Rotterdam, The Netherlands
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